Dataset Information

A genome-wide search for chromosomal loci linked to mental health wellness in relatives at high risk for bipolar affective disorder among the Old Order Amish.

ABSTRACT: Bipolar affective disorder (BPAD; manic-depressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant genetic component in the susceptibility to develop BPAD. To date, however, linkage studies have attempted only to identify chromosomal loci that cause or increase the risk of developing BPAD. To determine whether there could be protective alleles that prevent or reduce the risk of developing BPAD, similar to what is observed in other genetic disorders, we used mental health wellness (absence of any psychiatric disorder) as the phenotype in our genome-wide linkage scan of several large multigeneration Old Order Amish pedigrees exhibiting an extremely high incidence of BPAD. We have found strong evidence for a locus on chromosome 4p at D4S2949 (maximum GENEHUNTER-PLUS nonparametric linkage score = 4.05, P = 5. 22 x 10(-4); SIBPAL Pempirical value <3 x 10(-5)) and suggestive evidence for a locus on chromosome 4q at D4S397 (maximum GENEHUNTER-PLUS nonparametric linkage score = 3.29, P = 2.57 x 10(-3); SIBPAL Pempirical value <1 x 10(-3)) that are linked to mental health wellness. These findings are consistent with the hypothesis that certain alleles could prevent or modify the clinical manifestations of BPAD and perhaps other related affective disorders.

SUBMITTER: Ginns EI

PROVIDER: S-EPMC28077 | biostudies-literature | 1998 Dec

REPOSITORIES: biostudies-literature

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A genome-wide search for chromosomal loci linked to mental health wellness in relatives at high risk for bipolar affective disorder among the Old Order Amish.

Ginns E I EI St Jean P P Philibert R A RA Galdzicka M M Damschroder-Williams P P Thiel B B Long R T RT Ingraham L J LJ Dalwaldi H H Murray M A MA Ehlert M M Paul S S Remortel B G BG Patel A P AP Anderson M C MC Shaio C C Lau E E Dymarskaia I I Martin B M BM Stubblefield B B Falls K M KM Carulli J P JP Keith T P TP Fann C S CS Lacy L G LG Allen C R CR Hostetter A M AM Elston R C RC Schork N J NJ Egeland J A JA Paul S M SM

Proceedings of the National Academy of Sciences of the United States of America 19981201 26

Bipolar affective disorder (BPAD; manic-depressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant genetic component in the susceptibility to develop BPAD. To date, however, linkage studies have attempted only to identify chromosomal loci that cause or increase the risk of developing BPAD. To determine whether there could be protective alleles that prevent or reduce the risk of developing BPAD, si ...[more]

PMID: 9861003

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Project description:It is increasingly being recognized that physical interactions between distant chromosomal loci influence the expressivity of the genome. Thus, multiple enhancers may converge on a single gene promoter 1,2 and a single enhancer can stochastically loop to multiple promoters 3. Regulatory elements from neighboring domains or from other chromosomes may interact to generate chromatin structures poised for transcription4-8 or repression 9-11. However, a broader perspective on the formation and function of such networks remains largely unexplored. Using the high-resolution 4C (Circular Chromosome Conformation Capture) analysis, we identify here a genome-wide physical network between genomically imprinted domains impinging H19 imprinting control region (ICR). Sequences interacting with the H19 ICR constitutively map at or within most of known imprinted domains both in mouse embryonic stem cells and in vitro-derived embryoid bodies, despite distinct differences in chromatin environments. Moreover, all-to-all 3D DNA FISH analyses revealed that imprinted domains from 7 different chromosomes co-localize with each other in pair-wise patterns, highlighting the dynamic nature of these interactions. The observed interaction network is dependent on CTCF binding sites within the maternally inherited H19 ICR allele and delays reprogramming of epigenetic features at imprinted domains during male germline development. As other imprinted regions can interact with each other in an H19 ICR-dependent manner, the H19 ICR emerges as an organizer of chromosomal networks by specifically recognizing and reconfiguring imprinted domains. We propose that an ancient key regulatory region, such as the H19 ICR, gradually impacted epigenetic modifications via long-range interactions in the germline to facilitate the recruitment of imprinted genes and their formation in clusters during mammalian radiation. Furthermore, the perspective of epigenetic lesions de-stabilizing such chromosomal networks may advance our understanding of how quantitative traits influence human diseases, such as cancer.

Project description:Complementary and alternative medicine (CAM) in the form of vitamin and supplement use is increasingly prevalent in the United States. The interplay between CAM use and use of conventional medications is not well studied. We examined this issue in Old Order Amish (OOA), a population lacking several factors known to influence supplement use, whose culture and barriers to conventional medications may result in high rates of supplement use.We characterized the patterns of supplement use in OOA, including the extent to which CAM use aggregates in families, and assessed whether higher use of supplements is associated with lower medication use.We conducted a cross-sectional study of conventional medications and supplements in 2,372 adult Amish from the Lancaster County, PA, area. Data were collected through face-to-face interviews. Supplements were subcategorized as herbal vs vitamin/mineral supplements.Seventy-seven percent of all Amish adults reported current supplement use, whereas 22% reported medication use. Women used supplements more often and used more supplements than men, and familial aggregation of supplement use was stronger in family pairs involving women. Supplement use was associated with less medication use after controlling for age, sex, body mass index, and self-reported histories of hypertension, diabetes, and hyperlipidemia (adjusted odds ratio [OR] 0.96, 95% CI 0.92 to 1.00; P=0.047). This association was driven primarily by use of herbal supplements (adjusted OR 0.94, 95% CI 0.89 to 0.99; P=0.025) as vitamin/mineral supplements were not associated with different use of medication (adjusted OR 0.99, 95% CI 0.90 to 1.09; P=0.8). In analyses limited to cardiovascular medications and cardiovascular supplements in participants with hyperlipidemia, hypertension, or diabetes, supplement use was not associated with conventional medication use.OAA, particularly women, take dietary supplements much more frequently than they use conventional medications. Use of herbal supplements is associated with less use of conventional medications, whereas vitamin/mineral supplement use is not.

Dataset Information

A genome-wide search for chromosomal loci linked to mental health wellness in relatives at high risk for bipolar affective disorder among the Old Order Amish.

Publications

A genome-wide search for chromosomal loci linked to mental health wellness in relatives at high risk for bipolar affective disorder among the Old Order Amish.

Similar Datasets

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